The basic hypothesis underlying the proposed studies is that lipids found in the superficial layers of oral epithelium increase its diffusional resistance, and thereby, limit the penetration of a variety of potentially harmful agents including microbial toxins and enzymes, antigens from foods, and toxins and carcinogens from a variety of sources. Epithelial permeability varies regionally, and this is reflected in the distribution of certain diseases including leukoplakias and cancer. To establish an ultrastructural and molecular basis for understanding this regional variation in permeability and its relationship to oral health, several studies employing the well established porcine model system are proposed. Membrane-coated granules, the barrier precursors in both keratinized and nonkeratinized epithelia, will be isolated, and the lipids and some enzymes thought to function in barrier maturation will be characterized. Barrier layers will be isolated by tryptic digestion, and the compositions and structures of the lipids will be determined by chemical, chromatographic and spectroscopic methods. Barrier ultrastructure will be examined using a RuO4 method, and changes in organization, as well as in lipid composition and structure, accompanying the progressive perturbation of barrier function by essential fatty acid deficiency will be examined. The proposed studies include the first attempts to isolate and biochemically characterize membrane-coating granules from oral epithelium. This will provide basic information on lipid accumulation and the enzymatic basis for barrier assembly. A more complete knowledge of the barrier components and their modulation during barrier impairment would be useful in explaining the regional variation in permeability and disease occurrence and could ultimately be useful in explaining individual variation in susceptibility to disease. These studies are important in view of the possible role of impaired barrier function in the etiology of a variety of oral diseases and could ultimately lead to diagnostic methods and to strategies for preventing disease by augmenting barrier function.